Lets regenerate! The exci0ng life of a stem cell. Deepa Subramanyam, PhD Na0onal Centre for Cell Science, Pune. Slides adapted from CIRM

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1 Lets regenerate! The exci0ng life of a stem cell Deepa Subramanyam, PhD Na0onal Centre for Cell Science, Pune Slides adapted from CIRM

2 Our body is made up of different cells and organs. how are these made?

3 The first few days of life

4 What are stem cells? What are the different types of stem cells? Why should we study stem cells? What poten0al therapies could they provide? What are some of the challenges facing stem cell research?

5 All Stem Cells Can 1. Self- Renew 2. Differen0ate

6 Self- Renewal (symmetric cell division)

7 Differen0a0on (asymmetric cell division) Progenitor cell Stem cell Stem cell

8 Skin Cell Neuron (Brain Cell) Skin Progenitor Cell Neural Progenitor Cell Embryonic Stem Cell

9 Stem Cell Types Embryonic pluripotent: can form almost any cell type in the human body Tissue- Specific (Adult) mul0potent: can form only limited types of cells (blood, brain, liver, etc.) Induced Pluripotent engineered by scien0sts to act like embryonic stem cells

10 Day 1 In Vitro Development

11 Day 2 In Vitro Development

12 Day 2 In Vitro Development

13 Day 3 In Vitro Development

14 Day 4 In Vitro Development

15 In Vitro Development Day 5 Embryonic Stem Cells

16 This cell can form all of the cells in the human body This cell can form almost every cell type in the human body Fully mature

17 Human embryonic stem cells in culture

18 Fluorescent imaging of human embryonic stem cell colonies

19 Embryonic Stem- Cell Derived Heart Muscle Cells

20 Stem Cell Types Embryonic pluripotent: can form almost any cell type in the human body Tissue- Specific (Adult) mul0potent: can form only limited types of cells (blood, brain, liver, etc.) Induced Pluripotent engineered by scien0sts to act like embryonic stem cells

21 Adult stem cells are present in each organ for maintenance and repair Courtesy: Hans Clevers, TED talk, 2014

22 What Diseases Do Stem Cells Treat? Have the Poten0al to Treat? Currently Treat - Blood Diseases (including immune system disorders) - Gene0c metabolic disorders (very limited/experimental) - Tissue/organ replacement (very limited/experimental) Poten0al to Treat - Heart Disease - Neurological Diseases (Parkinson s, Alzheimer s, Hun0ngton s & others) - Stroke - Type 1 Diabetes - Macular Degenera0on (a common cause of blindness) - Cancer - HIV/AIDS - Spinal Cord Injury - Mul0ple Sclerosis - ALS (Lou Gehrig s Disease) - Liver Disease and more!

23 What can we do with stem cells?

24 Bone Marrow (Hematopoie0c Stem Cell) Transplant Example of a 0ssue- specific stem cell therapy

25 Making mini- organs from adult stem cells

26 Making mini- brains from stem cells Lancaster et al, Nature; 2013

27 Tissue- specific (adult) stem cells are powerful and promising! Why do researchers study embryonic stem cells? Tissue- specific stem cells are limited in their differen0a0on poten0al (blood à blood) Stem cells from some 0ssues are inaccessible Some 0ssue- specific stem cells don t self- renew well Some 0ssues may not have stem cells!

28 Stem Cell Types Embryonic pluripotent: can form almost any cell type in the human body Tissue- Specific (Adult) mul0potent: can form only limited types of cells (blood, brain, liver, etc.) Induced Pluripotent engineered by scien0sts to act like embryonic stem cells

29 But what about stem cells for myself?

30 We can imagine a ball rolling down a hill, but back upwards? Is it possible to take a cell that is already performing a specific function and take it back to a state where it does not have a fixed role aka stem cell state?

31 But how can we get stem cells from ourselves? Is there a magic solution? minus plus Stem cell plus minus?? Specialized cell Is this reversible? Can we subtract and add specific components to get back a stem cell?

32 Yes! Now I can make stem cells from my own body cells by addition and subtraction Stem cell Reprogramming!

33 Induced Pluripotent Stem (ips) Cells Gene0cally engineering new stem cells Virus engineered to express four key pluripotency genes à Pros: No embryos required No immune rejec0on? Disease in a dish? Skin cells Cons: May not be = to ESCs Gene0cally engineered ips cells

34 What are some of the challenges facing embryonic stem cell research? Differen0a0on of stem cells into mature, func0onal cells Poten0al for tumor forma0on Immune rejec0on

35 2 Nobel prizes one for stem cells and one for reprogramming.

36 Summary Stem cells are of three types: embryonic, adult and induced pluripotent. Embryonic stem cells are derived from the embryo and can give rise to all cell types in the body. Adult stem cells are present in each organ and can give rise to cell types present in that specific organ. Induced pluripotent stem cells can be made for each individual and are the future of regenera0ve medicine.

37 A word of cau0on Scien0sts are s0ll in the process of understanding the behaviour of stem cells. Improper use of stem cells in unapproved therapies can result in serious consequences and can be dangerous. Almost all stem cell therapies are s0ll NOT approved, even though there are numerous adver0sements proclaiming successful use of stem cells to treat various diseases/disorders.

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39 Thank you!